Table 2.
Effects of shift work, circadian or sleep disturbances on autoimmune (skin) diseases.
| Disease | Skin manifestations | Findings in shift workers | Circadian findings | Sleep findings | Key cellular players | Involved neuroendocrine mediators |
|---|---|---|---|---|---|---|
| Skin-specific autoimmune diseases | ||||||
| Psoriasis | Erythematosquamous plaques; rarely pustular changes; nail psoriasis in 50% of patients | Higher risk of development (191) | Generally disturbed 24 h rhythm (192); rhythmic regulation of neutrophil traffic (193); symptoms show diurnal pattern (163); symptom severity peaks in the evening and at night (194) | Pruritus disrupts sleep (195); systemic increase of proinflammatory cytokines by sleep deprivation in mice (196); increased frequency of sleep disturbances (197) and fatigue (198) | Neutrophils (193); gamma-delta T cells (199) | Dysfunctional HPA-axis with reduced cortisol levels; prolactin levels tend to be higher in psoriasis than in controls (200, 201); disturbed circadian rhythm of melatonin (202) |
| Vitiligo | Whitening due to destruction of melanin (203) | No data available | Blood rhythms in NK cell activity are shifted (204, 205), CD4 T cell number rhythm disrupted (206) | Sleep disturbances; poor sleepers show a higher risk of vitiligo (207, 208) | NK cells, CD4 T cells (204, 205) | Stress mediators and melatonin (209) |
| Pemphigus | Blisters in epidermis and mucous membranes; positive Nikolsky sign (210) | No data available | No data available | Bidirectional relationship (211) | Autoreactive B cells (212) | Corticosteroids are used as common symptomatic treatment; stress is able to trigger phemphigus flares and can worsen symptoms (213) |
| Pemphigoid diseases | Subepidermal blisters; negative Nikolsky sign (210) | No data available | No data available | Sleep disturbances due to symptoms peaking at night (66, 67, 214) | Autoreactive B cells; neutrophils (124, 215, 216) | Corticosteroids are used as common symptomatic treatment (217) |
| Systemic autoimmune diseases | ||||||
| Connective tissue diseases | ||||||
| Systemic lupus erythematosus | Malar rash, photosensitivity, alopecia, livedo reticularis (218) | Higher risk of development (162) | Photosensitivity (218); symptoms show diurnal pattern (163); excessive daytime-fatigue, especially in the morning (219) | Sleep disorders increase the risk of disease development (161) | B cells, plasma cells, Tregs (220); oxidative stress caused by Th17 cells (221) | Dysfunctional HPA-axis with reduced cortisol levels and changes in prolactin (222) and melatonin (221, 223); adrenal insuffiency (224) |
| Systemic Sclerosis | Puffy fingers, skin fibrosis, skin ulcers, calcinosis cutis, teleangiektasia (225) | No data available | Altered prolactin rhythms (226); symptoms show diurnal pattern (163) | Poor sleep leads to enhanced skin thickness (227); therapeutic sleep can be used to ameliorate skin symptoms (228); fatigue (225) | Th2 cells, B cells, macrophages (229) | Lower cortisol (230) and melatonin levels (231); altered prolactin rhythm (226) |
| Sjögren’s syndrome | Xeroderma (232) | Higher risk of development (163) | Circadian disruption is enhancing disease onset and progression (164); symptoms show diurnal pattern (163); excessive daytime-fatigue (219) | Patients often suffer from excessive daytime sleepiness, fatigue, insomnia, nocturnal headaches and nocturnal sweats (178); sleep disorders increase the risk of disease development (161) | Memory B cells, marginal zone B cells, plasma blasts and plasma cells (233) | Hypofunctional HPA-axis resulting in lower basal ACTH and cortisol levels (234) |
| Vasculitis | Purpura; Behcets syndrome (235, 236) | No data available | Inadequate decrease of nocturnal blood pressure (237) | Fatigue (238) | Dendiritc cells, Th17 cells and macrophages (239) and B cells (240) | Melatonin is able to relieve vascular endothelial cell damage (185) |
| Arthritis | ||||||
| Rheumatoid arthritis | Rheumatoid nodules, Felty syndrome, rheumatoid vasculitis, pyoderma gangrenosum, rheumatoid neutrophilic dermatosis, interstitial granulomatous dermatitis, palisaded neutrophilic dermatitis (241) | Higher risk of development (161); independency of higher risk for development from socioeconomic factors, health behavior or psychological distress (243); development of sero-positive rheumatoid arthritis was especially increased in rotating shift work and day-oriented shift work, whereas increasing duration of permanent night shift appears to be protective against rheumatoid arthritis (33) | Symptoms show diurnal pattern (163); peak of symptoms between 02 and 04 AM (244); excessive daytime-fatigue, especially in the morning (219); Disruption of the circadian clock results in aberrant expression of inflammatory cytokines (e.g. IL-6) disruptions of the peripheral chondrocyte clock promotes catabolic processes in cartilage (245) | Sleep disorders increase the risk of disease development (161); fatigue as common symptom (163); sleep disturbances, poor sleep quality and decreased total sleep time are common in rheumatoid arthritis; short sleep duration is causally linked to an increased disease risk (165) | T cells (Th1, Th2, Th17, Treg), cells of the B cell compartment, macrophages (246) | Dysfunctional HPA-axis and altered circadian rhythm of cortisol (248) and melatonin (183) |
| Spondyloarthritis | Pyoderma gangrenosum, hidradenitis suppurativa (242) | Higher risk of development (161) | Symptoms show diurnal pattern (163); major peaks in the morning between 06 AM and 09 AM (166) | Sleep disorders increase the risk of disease development (161); disease is also by sleep disturbances (178) | IL-17 is a key mediator which is produced by a variety of cells such as Th17 cells, neutrophils and macrophages (247) | Increase in backpain at midnight might be related to lower melatonin levels in spondyloarthritis patients compare to healthy controls (249) |
| Inflammatory bowel disease | Pyoderma gangrenosum, hidradenitis suppurativa (242) | Higher risk of development (167, 168); risk factor for surgery in Crohn’s disease, but not in ulcerative colitis (172); extended and irregular shift work might be a risk for chronic inflammatory bowel disease (173) | Disruption of the circadian system increases the activity of the gut immune system and the release of inflammatory factors; diurnal oscillations of microbiota (170) | Sleep disturbances are risk factors for development of Crohn’s disease in children (171); increased risk for ulcerative colitis in people sleeping less than 6 h and more than 9 h per day (173) | (169) Crohn’s disease: Th2; ulcerative colitis: Th1; both: Th17, Treg (250) | Lower 24 h amplitude of plasma cortisol in ulcerative colitis (251), lower levels of melatonin in ulcerative colitis (184) |
| Celiac disease | Dermatitis herpetiformis; association to psoriasis, chronic urticaria, leukocytoclastic vasculitis, alopecia areata (252) | No data available | No data available | Data on the presence of insomnia and sleep disturbances in patients with celiac disease is heterogeneous (253–255). sleep disturbances as well as primary sleep disorders such as sleep apnoea improve under gluten-free diet (256, 257) | Th1 cells, cells of the B cell compartment (258) | No data on the role of neuroendocrine mediators in dermatitis herpetiformis |
| Thyroiditis | Myxedema (259) | Higher risk of development (32) | Downregulated BMAL1 and PER2 expression (175) | Often occurs together with obstructive sleep apnoea but unclear if cause or consequence (176) | Infiltration of T cells, which release inflammatory cytokines (260) | Significant decrease of serum melatonin levels (175) |
Overview of autoimmune diseases and the effects of shift work and the circadian rhythm. Abbreviations in order of apearance: HPA, Hypothalamus-pituitary-adrenal; NK, natural killer; Th, T helper; Tregs, regulatory T cells; ACTH, adrenocorticotropic hormone; ACPA, anti-citrullinated protein antibody; IL, interleukin; UC, ulcerative colitis No relevant results were available for mixed connective tissue disease, polymyositis or dermatomyositis.